The role of TNF-α in a murine model of Kawasaki disease arteritis induced with a Candida albicans cell wall polysaccharide

Mod Rheumatol. 2014 Jan;24(1):120-8. doi: 10.3109/14397595.2013.854061.

Abstract

Objectives: Various inflammatory cytokines, including tumor necrosis factor-α (TNF-α), have been reported to play roles in Kawasaki disease (KD). Recently, anti-TNF-α therapy was reported to show efficacy in patients who do not respond to high-dose intravenous immunoglobulin therapy. However, there are many gaps in our understanding of the role that TNF-α plays in the development of KD arteritis as well as whether anti-TNF-α therapy causes any histological changes in the arteritis. Accordingly, the present histopathological study was carried out to elucidate the inhibitory effect of anti-TNF-α therapy on vasculitis as well as the role of TNF-α in the development of vasculitis in a murine model of KD vasculitis.

Methods: We used two anti-TNF-α drugs (etanercept and infliximab) to treat a Candida albicans-induced murine model of KD vasculitis. We investigated the histopathological changes in terms of the incidence of vasculitis, the scope of lesions and the degree of inflammation.

Results: Administration of etanercept to the mice reduced not only the incidence of vasculitis but also the scope of lesions and the degree of inflammation.

Conclusion: Based on the histological findings, TNF-α is deeply involved in the development of vasculitis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / therapeutic use*
  • Arteritis / chemically induced
  • Arteritis / drug therapy*
  • Arteritis / pathology
  • Candida albicans
  • Disease Models, Animal
  • Etanercept
  • Immunoglobulin G / therapeutic use*
  • Infliximab
  • Mice
  • Mucocutaneous Lymph Node Syndrome / chemically induced
  • Mucocutaneous Lymph Node Syndrome / drug therapy*
  • Mucocutaneous Lymph Node Syndrome / pathology
  • Myocardium / pathology
  • Polysaccharides
  • Receptors, Tumor Necrosis Factor / therapeutic use*
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Antibodies, Monoclonal
  • Immunoglobulin G
  • Polysaccharides
  • Receptors, Tumor Necrosis Factor
  • Tumor Necrosis Factor-alpha
  • Infliximab
  • Etanercept